The prognostic and predictive role of 21-gene recurrence scores in hormone receptor-positive early-stage breast cancer

Over the past two decades, gene expression profiling of breast cancer has emerged as an important tool in early-stage breast cancer management. The approach provides important information on underlying biological mechanisms, breast cancer classification, future risk potential of developing recurrent metastatic disease, and provides beneficial clues for adjuvant chemotherapy in hormone receptor (HR) positive breast cancer. Of the commercially available genomic tests for breast cancer, the prognostic and predictive value of 21-gene recurrence score tests have been validated using both retrospective data and prospective clinical trials. In this paper, we reviewed the current evidence on 21-gene expression profiles for HR-positive HER2-negative early-stage breast cancer management. We show that current evidence supports endocrine therapy alone as an appropriate adjuvant systemic therapy for approximately 70% of women with HR-positive, HER2-negative, node-negative breast cancer. Evolving evidence also suggests that 21-gene recurrence scores have predictive values for node-positive breast cancer and that chemotherapy can be avoided in more than half of women with nodes 1 to 3 positive HR-positive breast cancer. Furthermore, retrospective data also supports the predictive role of 21-gene recurrence scores for adjuvant radiation therapy. A prospective trial in this area is ongoing.     

National survey on edentulism and its geographic distribution, among Mexicans 18 years of age and older (with emphasis in WHO age groups)

To determine the prevalence of edentulism in adults aged 18 years and older in Mexico and to describe its distribution in 20 of the 32 States in Mexico, highlighting the experience in the WHO age groups. A secondary analysis of the National Performance Evaluation Survey 2002-2003 (representative at the state level and part of the Word Health Survey) was undertaken. The sample design was probabilistic, stratified and through conglomerates. Data on dental conditions were available only for 20 of the 32 states of Mexico, leading to a total of 24 159 households (N = 54 638 654). The percentage of edentulism was determined as the proportion of subjects that self-reported complete loss of teeth. Data were analyzed using the SVY module for complex surveys in STATA 8.2. The mean age was 41.3 +/- 17.0 years (range 18-99). An estimated 6.3% (N = 3 437 816) of the population > or =18 years was edentulous. Lowest prevalences were observed in the states of Tlaxcala, Puebla and the Estado de Mexico with 3.4%, 3.8% and 4.5%, respectively. Highest prevalences were observed in San Luis Potosí, Colima, and Michoacán with 10.3%, 10.2% and 10.1%, respectively. Following the WHO age groups, the prevalence ranged from 2.4% in the 35-44 group through 25.5% in the 65-74 group. No obvious association between socio-economic and socio-demographic indicators at the state level and prevalence of edentulism was found. The prevalence of complete tooth loss observed in the present study varied greatly across states, although no straightforward association was found with socio-economic and socio-demographic indicators at the state level. This study could serve as a baseline to enable future evaluations of the oral status of Mexican adults and elders, following WHO age groups.     

Gradation of the Stress Response in Rainbow Trout Exposed to Stressors of Different Severity: The Role of Brain Serotonergic and Dopaminergic Systems

After an intense acute stressor, fish develop a metabolic and behavioural response that usually lasts for several hours. Brain monoaminergic systems, particularly the serotonergic system, appear to play a key role in the central regulation of the stress response. However, the influence of stressor severity on brain monoaminergic systems and on the induced stress responses is yet poorly understood. We hypothesise that serotonergic system could have a direct role in the integration of sensory information during stressor exposure and in the organisation of the subsequent integrated stress response. According to our hypothesis, a low stressor intensity would induce a low response of brain serotonergic system and therefore stress responses of low magnitude and duration. To test this hypothesis, we exposed fish to handling disturbance for 5 s, 15 s or 3 min. We sampled fish at 0 (controls), 3, 15, 45 and 240 min after the start of the stress protocol. Brain levels of serotonin, dopamine and their respective main oxidative metabolites were quantified, along with plasma levels of stress markers (catecholamines, cortisol, glucose and lactate). Regarding stress markers, the 5‐s and 15‐s stress protocols induced similar and relatively low elevations in all parameters assessed. As expected, the 3‐min protocol induced responses of a higher intensity and duration in all plasma parameters. Interestingly, the alterations of brain monoaminergic systems did not follow the same trend. The three stress protocols induced increases in the serotonergic activity in all brain regions analysed (hypothalamus, telencephalon and medulla oblongata), independently of the duration of the handling disturbance, whereas the effects on the dopaminergic system were minor and brain region‐dependent. These data suggest that the brain serotonergic system, although likely involved in the recognition of the stressor stimuli, is not the only actor determining the magnitude and duration of the acute stress response in trout.     

Extracts of Renealmia alpinia (Rottb.) MAAS Protect against Lethality and Systemic Hemorrhage Induced by Bothrops asper Venom: Insights from a Model with Extract Administration before Venom Injection

Renealmia alpinia (Rottb.) MAAS, obtained by micropropagation (in vitro) and wild forms have previously been shown to inhibit some toxic activities of Bothrops asper snake venom if preincubated before injection. In this study, assays were performed in a murine model in which extracts were administered for three days before venom injection. R. alpinia extracts inhibited lethal activity of B. asper venom injected by intraperitoneal route. Median Effective Dose (ED₅₀) values were 36.6 ± 3.2 mg/kg and 31.7 ± 5.4 mg/kg (p > 0.05) for R. alpinia wild and in vitro extracts, respectively. At a dose of 75 mg/kg, both extracts totally inhibited the lethal activity of the venom. Moreover, this dose prolonged survival time of mice receiving a lethal dose of venom by the intravenous route. At 75 mg/kg, both extracts of R. alpinia reduced the extent of venom-induced pulmonary hemorrhage by 48.0% (in vitro extract) and 34.7% (wild extract), in agreement with histological observations of lung tissue. R. alpinia extracts also inhibited hemorrhage in heart and kidneys, as evidenced by a decrease in mg of hemoglobin/g of organ. These results suggest the possibility of using R. alpinia as a prophylactic agent in snakebite, a hypothesis that needs to be further explored.     

Impact of socio-demographic,socioeconomic, and water variables on dental fluorosis in adolescents growing up during the implementation of a fluoridated domestic salt program

The objective of this study is to determine the impact of socio-demographic, socioeconomic, and other risk indicators on dental fluorosis (DF) among Mexican adolescents. A cross-sectional study was carried out in 1,538 adolescents 12 and 15 years of age in semi-rural communities located at high altitude (>2,000 m) and with high concentration of fluoride in water (1.38–3.07 ppm) in Hidalgo, Mexico. DF was determined by means of Dean’s Index and all teeth were examined. Remaining variables were collected using a questionnaire. The adjusted final model was performed using ordered logistic regression. After adjusting for sex, the variables associated with DF were (p < 0.05): being 12 years old (OR = 1.10) versus 15 years old; having lived the first 6 years of life in El Llano (3.07 F ppm) (OR = 3.19) or San Marcos (1.38 F ppm) (OR = 1.63) versus Tula (1.42 F ppm); having public (OR = 1.35) or private health insurance (OR = 1.36) versus those without insurance; belonging to the lower quartiles of socioeconomic position (SEP) [1st quartile (OR = 2.48), 2nd quartile (OR = 1.81), 3rd quartile (OR = 1.49)] versus the highest quartile; having drunk tap water (OR = 1.83) or from a well or spring (OR = 2.30) versus those who drank water purchased in large containers or bottles. Demographic and socioeconomic variables were associated with DF. While better SEP appeared to play an important role in DF, a pattern of water intake associated with water purchased in large containers or bottles (which have different connotations to the use of bottled water in industrialized Western countries) did reduce DF risk in these high fluoride content, high altitude communities.     

Locking versus non-locking plating system in the treatment of mandibular fractures: A randomized comparative study

To evaluate fracture stability and complications such as infections, need for hardware removal, malunion, and nonunion when using 2.0-mm locking plating system in fixation of mandible fractures and to compare these to those associated with the 2.0-mm non-locking plating system.A prospective clinical study was conducted in a cohort of mandible fracture patients who were randomly assigned to two groups. Patients in the non-locking group were treated with 2.0-mm non-locking plating system, and those in locking group were treated with 2.0-mm locking plating system. Fracture stability, need for maxillomandibular fixation (MMF) and postoperative complications were assessed and compared.A total of 60 patients (30 in each group) were recruited. Significant differences were found between the two groups with respect to postoperative fracture stability (P = 0.001) and need for MMF (P = 0.005). Multivariate analysis revealed that type of fixation was not the only dependent variable which affected fracture stability. There were no significant differences in postoperative complications between the two groups.The 2.0-mm locking plating system provides greater stability and early functional restoration than the 2.0-mm non-locking plating system, with similar rates of postoperative complications. Thus, it can be used as a reliable and effective treatment modality for treating mandibular fractures.